Trifluoroacetic acid → (S)-1-methyl-10-((S)-3-methyl-pyrrolidin-3-yl)-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one

HRID 519157Notes

Reaction equation

HRID 519157 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@@:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2/[CH:29]=[CH:30]/OCC)[O:25][CH2:24][C:23]2[N:18]3[C@@H:19]([CH3:35])[C:20](=[O:34])[NH:21][N:22]=2)([CH3:13])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:35][C@H:19]1[C:20](=[O:34])[NH:21][N:22]=[C:23]2[N:18]1[C:17]1[CH:16]=[C:15]3[N:14]([C@@:10]4([CH3:13])[CH2:11][CH2:12][NH:8][CH2:9]4)[CH:30]=[CH:29][C:28]3=[CH:27][C:26]=1[O:25][CH2:24]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86727549(S)-3-[(S)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 86727551(S)-1-methyl-10-((S)-3-methyl-pyrrolidin-3-yl)-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-oneYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3-[(S)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.115 g, 0.273 mmol) in DCM (2 mL) was added TFA (1 mL) and the reaction mixture was stirred at ambient temperature for 1 h. The solvent was removed in vacuo and the residue was purified by prep-TLC (eluting with 15% MeOH in DCM) to give (S)-1-methyl-10-((S)-3-methyl-pyrrolidin-3-yl)-3,5-dihydro-10H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one (0.020 g, 25%, SFC (Table 1, Method 53) Rt=1.81 min) as a white solid. 1H-NMR (400 MHz, methanol-d4) δ 7.41 (d, J=3.2 Hz, 1H), 7.25 (s, 1H), 7.22 (s, 1H), 6.49 (d, J=3.2 Hz, 1H), 5.11 (q J=6.8 Hz, 1H), 4.62-4.54 (d, J=13.6 Hz, 2H), 4.16-4.09 (m, 1H), 3.88-3.82 (m, 1H), 3.67-3.47 (m, 2H), 3.10-2.97 (m, 1H), 2.71-2.59 (m, 1H), 1.78 (s, 3H), 1.49 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 5) Rt=1.916 min; MS m/z: 340 [M+1]+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by prep-TLC (eluting with 15% MeOH in DCM)

Sources & evidence

ORD record
ord-374ae90497734efbbd27fe71c5e3df9e
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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